Allogeneic Bone Marrow Mesenchymal Stromal Cell Transplantation Induces Dentin Pulp Complex-like Formation in Immature Teeth with Pulp Necrosis and Apical Periodontitis.

INTRODUCTION: Dental pulp regeneration is challenging in endodontics. Cellular therapy is an alternative approach to induce dental pulp regeneration. Mesenchymal stromal cells (MSCs) have the capacity to induce dental pulp-like tissue formation. In this study, we evaluated the capacity of allogeneic bone marrow MSCs (BM-MSCs) to regenerate pulp following necrosis and apical periodontitis in children's permanent immature apex teeth. METHODS: Patients aged 8 to 12 years with pulp necrosis and apical periodontitis were evaluated. The study included 15 teeth (13 incisors and 2 molars) from 14 patients (8 boys and 6 girls). Radiographic evaluation showed periapical radiolucency and immature apex teeth. There was no response to cold or electric pulp testing. The root canal of each tooth was cleaned, shaped, and Ca(OH)2 used as an interappointment medication. Cryopreserved allogeneic BM-MSCs were thawed, expanded, incorporated into preclotted platelet-rich plasma, and implanted into the tooth's pulp cavity. They were sealed with bioceramic cement and composite. Sensibility, apical foramen, calcium deposits within the root canal, and resolution of periapical lesions were evaluated in each tooth over the following 12 months. RESULTS: Based on 9 variables established for dental pulp-like tissue regeneration, all MSC-treated teeth showed evidence of successful regeneration. Clinical and radiographic evaluation of the treated teeth showed periapical lesion healing, sensitivity to cold and electricity, decreased width of the apical foramen, and mineralization within the canal space. CONCLUSIONS: Transplantation of allogeneic MSCs induces the formation of dental pulp-like tissue in permanent immature apex teeth with pulp necrosis and apical periodontitis. Implant of MSCs constitutes a potential therapy in regenerative endodontics in pediatric dentistry. Future studies incorporating a larger sample size may confirm these results.

Wound healing by transplantation of mesenchymal stromal cells loaded on polyethylene terephthalate scaffold: Implications for skin injury treatment.

BACKGROUND: Several clinical studies have shown that cellular therapy based on mesenchymal stromal cells (MSCs) transplantation may accelerate wound healing. One major challenge is the delivery system used for MSCs transplantation. In this work, we evaluated the capacity of a scaffold based on polyethylene terephthalate (PET) to maintain the viability and biological functions of MSCs, in vitro. We examined the capacity of MSCs loaded on PET (MSCs/PET) to induce wound healing in an experimental model of full-thickness wound. METHODS: Human MSCs were seeded and cultured on PET membranes at 37 °C for 48 h. Adhesion, viability, proliferation, migration, multipotential differentiation and chemokine production were evaluated in cultures of MSCs/PET. The possible therapeutic effect of MSCs/PET on the re-epithelialization of full thickness wounds was examined at day 3 post-wounding in C57BL/6 mice. Histological and immunohistochemical (IH) studies were performed to evaluate wound re-epithelialization and the presence of epithelial progenitor cells (EPC). As controls, wounds without treatment or treated with PET were established. RESULTS: We observed MSCs adhered to PET membranes and maintained their viability, proliferation and migration. They preserved their multipotential capacity of differentiation and ability of chemokine production. MSCs/PET implants promoted an accelerated wound re-epithelialization, after three days post-wounding. It was associated with the presence of EPC Lgr6+ and K6+. DISCUSSION: Our results show that MSCs/PET implants induce a rapid re-epithelialization of deep- and full-thickness wounds. MSCs/PET implants constitute a potential clinical therapy for treating cutaneous wounds.

The effects of mesenchymal stromal cells and platelet-rich plasma treatments on cutaneous wound healing.

Cellular therapy and platelet-rich plasma (PRP) have been used as a treatment for skin wounds. Previous evidence has shown that mesenchymal stromal cells (MSC) may improve skin wound healing. In contrast, contradictory effects have been reported by using PRP treatment on skin wound healing. However, there is evidence that PRP constitutes an excellent scaffold for tissue engineering. In this work, we aim to study the effect of MSC on skin wound healing. We used an experimental murine model of full-thickness wounds. Wounds were treated with human bone marrow-MSC contained in a PRP clot. Untreated or PRP-treated wounds were used as controls. Wound healing was evaluated by macroscopic observation and histological analysis at day 7 post-wounding. Immunohistochemical studies were performed to detect the presence of epithelial progenitor cells (EPC) and the expression of basic fibroblast growth factor (bFGF). MSC/PRP implantation induced a significant wound closure and re-epithelialization as compared with the controls. Increase of CD34+ cells and bFGF was observed in the wounds treated with MSC/PRP. Our results show that MSC included in PRP clot induce cutaneous wound repair by promoting re-epithelialization, migration of EPC and expression of bFGF. PRP alone does not exert a significant effect on wound healing. Our results support the possible clinical use of MSC in PRP scaffold as potential treatment of skin wounds.

Evaluation of epithelial progenitor cells and growth factors in a preclinical model of wound healing induced by mesenchymal stromal cells.

BACKGROUND: Skin wounds continue to be a global health problem. Several cellular therapy protocols have been used to improve and accelerate skin wound healing. Here, we evaluated the effect of transplantation of mesenchymal stromal cells (MSC) on the wound re-epithelialization process and its possible relationship with the presence of epithelial progenitor cells (EPC) and the expression of growth factors. METHODS: An experimental wound model was developed in C57BL/6 mice. Human MSCs seeded on collagen membranes (CM) were implanted on wounds. As controls, animals with wounds without treatment or treated with CM were established. Histological and immunohistochemical (IH) studies were performed at day 3 post-treatment to detect early skin wound changes associated with the presence of EPC expressing Lgr6 and CD34 markers and the expression of keratinocyte growth factor (KGF) and basic fibroblast growth factor (bFGF). RESULTS: MSC transplantation enhanced skin wound re-epithelialization, as compared with controls. It was associated with an increase in Lgr6+ and CD34+ cells and the expression of KGF and bFGF in the wound bed. CONCLUSION: Our results show that cutaneous wound healing induced by MSC is associated with an increase in EPC and growth factors. These preclinical results support the possible clinical use of MSC to treat cutaneous wounds.